INTERCHANGEABILITY – DESIGNATION MATTERS
What is interchangeability?
Not all biosimilars are considered interchangeable!
An interchangeable product is a biosimilar for which the sponsor has demonstrated that the biosimilar can be expected to produce the same clinical result as the reference product in any given patient.1
For an interchangeable product administered to a patient more than once, the sponsor has also demonstrated that the risk in terms of safety and diminished efficacy of switching between the interchangeable product and a reference product will not be greater than the risk of using the reference product without such switching.1
What does it take for a biosimilar to be designated interchangeable?
Biosimilars that are designated as interchangeable have demonstrated that they produce the same clinical results as the reference product. Without this designation, a biosimilar’s clinical efficacy may vary from the reference product, though, by definition, not with a “meaningful difference.”2,3
The FDA requires switching studies to further assess the risk, in terms of safety and diminished efficacy, of alternating or switching between the products (see Figure 1). Switching between a biosimilar and reference product can increase the risk for antidrug antibodies and immunological reactions and decrease drug efficacy.4
Draft guidance by the FDA describes how a switching study or studies should evaluate changes in treatment that result in two or more alternating exposures (switch intervals) to the proposed interchangeable product and to the reference product.2,3
Key endpoints of these studies include pharmacokinetics, pharmacodynamics, and immunogenicity
For biological products that are not intended to be administered to an individual more than once, FDA expects that switching studies would generally not be needed.3
What are the benefits of a biosimilar receiving interchangeability designation?
Without interchangeability, prescribers must choose a specific biosimilar or reference biologic by name, which limits the potential for biosimilars to gain market share and compete on price5
With this designation, in the United States, pharmacies can dispense interchangeable biosimilars without needing prescribers’ authorization for the change, subject to state law6 (Click here to obtain the most current information about state laws on biologics and biosimilar substitution)
Understanding the difference between switching, substitution, and interchangeability7
Switching: A physician-driven decision to change one medication for another with the same therapeutic intent
Substitution: Pharmacy dispensing a generic equivalent for a branded medication, when “brand only” is not called out by the prescribing physician
Interchangeability: Pharmacy dispensing (US rule only) of an FDA-designated interchangeable biosimilar over a branded product
Biosimilars action plan: balancing innovation and competition. U. S. Food & Drug Administration website. https://www.fda.gov/downloads/
Drugs/ DevelopmentApprovalProcess/ HowDrugsareDevelopedandApprove d/ApprovalApplications/ TherapeuticBiologicApplication s/Biosimilars/UCM613761.pdf. Updated July 2018. Accessed July 25, 2018.
Background information: lists of licensed biological products with reference product exclusivity and biosimilarity or interchangeability evaluations (Purple Book). U.S. Food & Drug Administration website. https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/therapeuticbiologicapplications/biosimilars/ucm411424.htm. Updated March 5, 2015. Accessed February 16, 2018.
Considerations in demonstrating interchangeability with a reference product: guidance for industry. U.S. Food & Drug Administration website. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM537135.pdf. January 12, 2017. Accessed February 16, 2018.
Barlas S. FDA guidance on biosimilar interchangeability elicits diverse views. P&T. 2017;42:509-512.
Mulcahy AW, Hlávka JP, Case SP. Biosimilar cost savings in the United States. RAND Corporation website. https://www.rand.org/content/dam/rand/pubs/perspectives/PE200/PE264/RAND_PE264.pdf. Accessed February 16, 2018.
Prescribing biosimilar and interchangeable products. U.S. Food & Drug Administration website. https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/therapeuticbiologicapplications/biosimilars/ucm580430.htm. Updated October 23, 2017. Accessed February 16, 2018.
Stanton D. Biosimilar interchangeability: do you know your switching from your substitution? BioPharma Reporter website. March 21, 2017. https://www.biopharma-reporter.com/Article/2017/03/21/Biosimilr-switching-interchangeability-and-substitution-the-EU-view?utm_source=copyright&utm_medium=OnSite&utm_campaign=copyright. Accessed April 4, 2018.